The fifth and final patient in the phase 1/2a clinical trial of TT-034, a ddRNAi-based therapeutic to treat hepatitis C virus infection, has been dosed, according to a news release from Benitec Biopharma Limited.
The fifth and final patient in the phase 1/2a clinical trial of TT-034, a
ddRNAi-based therapeutic to treat hepatitis C virus infection, has been
dosed, according to a news release from Benitec Biopharma Limited.
at the Duke Clinical Research Unit of Duke Clinical Research Institute
is an open-label dose escalation study that evaluates the safety and
activity of single doses of TT-034 (Benitec), a potential treatment for
HCV with a single-dose administration, in patients with chronic HCV
genotype 1 infection who have failed previous treatments, according to
the Duke Clinical Research Unit website. The trial consists of 14
patients in five sequential dose cohorts.
that was a half-log higher than patients dosed in the first cohort,
according to the release. The dose level was still below the
concentration expected to inhibit HCV viral replication, according to the release.
SOURCE Benitec Biopharma Limited
Biopharma Limited (ASX: BLT, OTC: BTEBY) is pleased to advise that the
third patient in its Phase I/IIa clinical trial of TT-034 for hepatitis C
was dosed earlier today at the Duke Clinical Research Unit (USA).
This is a significant step for this “first in man” study, and follows
review of the collective data from the first two patients by the
independent Data Safety Monitoring Board (DSMB). The DSMB determined
that the patients from the first dosing cohort were clear of any
significant treatment-related adverse events.
newly dosed patient is the first to receive the increased dose of
TT-034 (1.25 x 10^11 vg/kg, a concentration that is a half log higher
than the doses administered in the first cohort). While TT-034 is
designed as a potential “one-shot” cure for hepatitis C, the current
dose is still below that expected to inhibit viral replication and data
from the second dosing cohort are therefore expected to serve primarily
as a further safety assessment.
with previous patients, the newly dosed patient will be monitored for
six weeks and results will be reviewed by the DSMB. Should the results
indicate appropriate safety outcomes, the DSMB is expected to recommend
that the remaining two patients in the second cohort be dosed. It is
aimed to dose both at approximately the same time. The trial sites at
Duke Clinical Research Unit and University of California San Diego have identified a number of patients who have passed initial screening who can be prepared in anticipation of this outcome.
is a ddRNAi-based therapeutic, designed to treat and potentially cure
hepatitis C (HCV) with a single administration. TT-034 targets the
hepatitis C viral RNA at three separate, highly conserved sites. As such
it acts as a “triple therapy” even though it is a monotherapy, and
minimizes the ability of the virus to mutate and escape the therapy.
Once it reaches the liver cells, it enters the nucleus and produces
three separate short hairpin RNAs continuously for the lifetime of the
cell. Thus TT-034 has the potential to not only treat the existing HCV
infection, but also to guard against reinfection for months to years
without the need to re-treat. TT-034 safety and efficacy has been tested
extensively in pre-clinical in vivo studies with no adverse effects
observed at therapeutic doses.
Biopharma Limited is an ASX-listed biotechnology company (ASX: BLT;
OTC: BTEBY), which has developed a patented gene silencing technology
called DNA-directed RNA interference (ddRNAi). ddRNAi has the potential
to produce ‘single-shot’ treatments and even cures for a range of
chronic and life- threatening human conditions. Based in Sydney, Australia, with labs in Hayward CA
(USA) and collaborators and licensees around the world, the company is
developing ddRNAi-based therapeutics for diseases including hepatitis C
and B, drug resistant lung cancer and wet age-related macular
degeneration. Benitec has licensed ddRNAi to other biopharmaceutical
companies for human therapeutic applications including HIV/AIDS,
Huntington’s Disease, cancer, chronic neuropathic pain and retinitis
pigmentosa. For more information visit www.benitec.com.
SOURCE Benitec Biopharma Limited
SYDNEY, May 29, 2014 /PRNewswire/ — RNAi-based therapeutics company,
Benitec Biopharma Limited (asx:BLT) is pleased to announce that it has
dosed the first patient in its ‘first in man’, Phase I/IIa clinical
trial for TT-034, a ddRNAi-based therapeutic, designed to treat and
potentially cure hepatitis C (HCV) with a single injection.
commencement of this clinical trial of TT-034 represents a landmark in
the Company’s history. The trial is the first time Benitec’s gene
silencing technology, ddRNAi, has been used systemically in patients.
can be used safely in patients with HCV. Preclinical work in non-human
primates demonstrated very low toxicity results at therapeutically
relevant doses, and we’re hopeful that we will see the same favourable
tolerability in humans. In addition, we will be able to assess the
impact of TT-034 treatment on HCV viral load in these patients, and this
important efficacy marker constitutes one of the secondary endpoints of
study in a total of 14 patients chronically infected with HCV genotype
1. Initial patient cohorts will be treated with a sub-therapeutic dose
of TT-034 to ensure that there are no unexpected safety concerns, before
proceeding to higher, potentially therapeutic doses.
is independent of Benitec, will carefully assess the data from each
patient, in particular the safety data. The DSMB assessment will occur
after the first patient in each cohort and between cohorts, and will
determine the timing of each subsequent dosing.
The gene-silencing technology, developed by CSIRO, will be used on 14
US patients suffering from hepatitis C, in the hope it can fight off
If proved safe and effective, the treatment could allow doctors to directly place medication into a patient’s genes.
company Benitec Biopharma gained approval from the US Food and Drug
Administration for a trial of the technology, known as DNA Directed RNA
Interference. The trial will be run at Duke University and the
University of California over the next 18 months.
Researchers at Britain’s University of Westminster have developed a
means to test a cure for hepatitis C, a deadly liver disease that causes
350,000 deaths around the world each year.
Hepatitis C is caused by the hepatitis C virus HCV and, for the first
time, a drug that is believed to cure the disease is being tested on
humans. The drug, TT-034, was developed using gene therapy by an
Australian company, Benitec Biopharma.
SYDNEY, April 15, 2013 /PRNewswire/ — RNAi-based therapeutics company
Benitec Biopharma Limited (ASX Code: BLT) today announced the selection
of the University of California, San Diego (UCSD), Health Sciences as
the second site for its upcoming phase I/II first-in-man trial for
TT-034 in Hepatitis C infections (HCV). Benitec previously announced the
selection of Duke Clinical Research Unit as the other site. TT-034 is
being developed as a potential “one-shot-cure” for HCV.
A consultant and sub-principal investigator for the study from UCSD
Health Sciences will be Robert Gish, M.D., clinical professor of
Medicine and medical director of Hepatology. Dr. Gish is a renowned
hepatitis researcher with previous experience using RNAi based
therapeutics for HCV. He has over 500 publications in the field and is a
fellow of the American College of Physicians and the American
Association for the Study of Liver Disease.
“I look forward to working with Benitec and Duke University on this
important program,” Dr. Gish commented. “This is the first time that
this therapeutic modality is being tested in humans, and if it is
successful I believe it can be a significant step forward, not only for
HCV treatment but potentially also as a treatment modality for Hepatitis
The principal investigator for the study at UC San Diego is David
Wyles, M.D., associate professor of Medicine at the UC San Diego
AntiViral Research Center, the clinical research site that will be
conducting the trial. His research interests include the laboratory
evaluation of new antiviral therapies for HCV, drug resistance to HCV
antivirals, and HCV viral fitness.
Peter French, Ph.D., chief executive officer of Benitec said, “We are
elated that UC San Diego and Dr. Gish will participate in this study. We
now have two top clinical research teams working with Benitec on this
trial. This constellation of expertise will greatly benefit our HCV
program and can help demonstrate the power of our ddRNAi technology in
the clinic. Having our two clinical centers in place moves us a step
closer to initiating the Phase I/II clinical trial, which we expect to
occur during the second half of 2013.”
The phase I/II clinical trial is an open-label dose escalation study
to evaluate the safety and activity of single doses of TT-034 in
patients with chronic HCV genotype 1 infection who have failed previous
treatments. The trial is expected to involve 14 patients in 5 sequential
dose cohorts. Additional consolidation cohorts may be added during the
study to confirm the results of the trial. The primary safety endpoints
are dose limiting adverse events. The primary end points are serum viral
load reduction and degree of hepatocyte transduction (measured through
liver biopsies). There is a pre-specified interim read on safety and
activity within months of trial commencement.
TT-034 is a potentially transformative therapeutic that is intended to
provide a “one-shot-cure” for Hepatitis C with a single injection.
TT-034 works through RNA interference (RNAi), which is a naturally
occurring regulatory process in cells that acts to “silence” genes after
they have been transcribed from DNA into messenger RNA. Benitec’s
proprietary ddRNAi approach involves the introduction of a DNA vector
that produces short hairpin RNAs (shRNAs) that are processed by the cell
into siRNAs. This approach emulates the cell’s own gene silencing
mechanism and provides long term activity (months). Moreover, the virus
vector used to deliver the TT-034 construct, an engineered
non-replicating adeno-associated virus (AAV8), targets almost
exclusively liver cells (where HCV replicates). TT-034 is further
designed to prevent viral escape through mutations (a major problem for
most HCV drugs) by using three different shRNAs to simultaneously target
three separate highly conserved regions in the HCV genome. In mice and
monkeys, TT0-034 has been shown to transduce 100% of hepatocytes in the
liver and provide high shRNA activity for 180 days (the duration of the
studies), without adverse effects.